FR2555167A1 - NEW CHALCONE DERIVATIVES AND ULTRA-VIOLENT ABSORBERS COMPRISING THEM - Google Patents

Abstract

THE SUBJECT OF THE INVENTION IS A CHALCONE DERIVATIVE AND UV RAY ABSORBERS CONTAINING SUCH A DERIVATIVE. THIS DERIVATIVE MEETS FORMULA I: (CF DRAWING IN BOPI) IN WHICH R H OR METHYL AND R RADICAL HYDROCARBON ALIPHATIC LINEAR OR BRANCHED IN C. THESE ABSORBERS IN THE FORM OF CREAMS, SOLUTIONS, OILS, PENCILS, EMULSIONS, ETC. CONSTITUTE EFFECTIVE PROTECTION AGAINST BREATH AND SUN BURNS.

Description

The present invention relates to novel chalcone derivatives and

  ultraviolet absorbers comprising these derivatives.

  UV rays are known to produce various changes in the skin. From the dermatological point of view, UV rays, on the basis of their wavelengths, are generally classified as long wavelength UV rays of 400 to 320 nm, medium wavelength UV rays of

  320 to 290 nm and UV rays short wavelength 290 nm (short wave).

  These rays are respectively called UV-A UV-B and UV-C.

  Usually, a typical source of UV radiation to which humans are exposed is sunlight. UV rays from sunlight that can reach the ground surface are UV-A and UV-B. UV-C is absorbed by the ozone layer and rarely reaches the surface of the soil. Of the UV rays that reach the soil surface, UV-B can produce erythema and blisters and lead to skin changes such as accelerated melanin formation, pigmentation and the like by irradiating the skin with light amounts above a certain

  riveau. On the contrary, it was considered until now that UV-A

  there was no noticeable change in the skin. However, it has recently been observed by electron microscopic and histochemical techniques that the skin undergoes modifications even by irradiation with UV-A. In particular, the UV-A energy, different from that of UV-B, even reaches the inner layers of the skin and causes slight, chronic changes in the elastic fibers of the walls of the blood vessels and

  connective tissues. These modifications are considered to be at the origin

  accelerated aging of the skin. It is also known that UVA has a skin melanization action (melanization limited in time)

  immediately after irradiation of the skin and that they act to increase

  ter the degenerating action of UV-B on the skin. UV-A is therefore considered to be one of the factors of development and exacerbation of chloasmas

and freckles.

  As is apparent from the foregoing, it is important to protect the skin not only from UV-B but also from UV-A in the protection of the skin against the onset of aging and against development.

  and the exacerbation of chloasmas and freckles.

  However, studies concerning the action of UV-A on the skin are only fairly recent, and only a small number of substances capable of absorbing UV-A are currently known when they are applied to the skin.

  skin, including dibenzoylmethane derivatives and cindic acid derivatives.

  German Patent Publication Nos. 2,728,241 and 2,728,243 and Japanese Patent Applications Nos. 51-61641, 52-46056, 57-59840 and 57-197209). Accordingly, there is a strong demand for the development of protective agents capable of absorbing harmful UV-A in order to effectively protect human skin from these. Such protective agents must

meet the following requirements.

  1) Maximum absorbing power at a wavelength close to 350 nm.

  2) High molar absorptivity coefficient at the wavelength above

above.

  3) Low absorptivity of visible light since the color

  ration of cosmetic compositions is not desirable, that is to say that

  must be close to zero (O) above 400 nm.

  4) Strong stability with regard to heat and light.

  ) No toxic, irritating or other harmful action to the skin.

  6) Good compatibility with cosmetic substrates.

  7) Little risk of percutaneous absorption when applied to the skin and disposal, eg by transpiration, or continuation

real efficiency.

  The Applicant has carried out extensive studies and found that

  Some types of chalcone derivatives, well known as one of the components of plants, can meet the above requirements and can

  therefore effectively protect from UV-A.

  Accordingly, the present invention aims to provide new chalcone derivatives, as well as UV absorbers which include these new compounds.

of chalcone.

  According to the invention, it is possible to achieve the above objects with chaleone derivatives corresponding to the general formula (I):

O O

  wherein R1 represents a hydrogen atom or a methyl group and R2 represents an aliphatic hydrocarbon group

  straight or branched chain containing from 2 to 24 carbon atoms.

  The single figure of the appended drawing is a graph showing the SPF values of products 1 to 7 according to the invention and comparative products 1 and 2.

  The new chalcone derivatives according to the invention may be

  trimmed by known techniques. In particular, as it is indi-

  in the following reaction sequence, 4-methoxybenzaldehyde is

  hyde and 4-hydroxyacetophenone to a condensation reaction to obtain 1C a 4-aleoxy-4'-hydroxychalcone (II), then acylation is carried out to obtain the desired derivative of chalcone (I)

o ±

{I H or OH-

  R1O% -CHO + CH3C-e -OH ondensate n Condensation (trans) O il R2COC1 or (R2CO) 2 2RiO = -fCH = CH-Ci "OH base R10- (base (II)

O O

R10__CH: CH-C / O -C-R2

(1)

  sequence in which R1 and R2 have the same meanings as above.

  The starting hydroxychalcone (II) in which R1 is a group

  Methyl is known (Szell et al., Can J. Chem., 42, 2417 (1964), Can.

  J. Chem., 43, 2134 (1965), D. Vorlander, Chem., Ber., 58, 118 (1925), G. Sipos et al., Chem. Abstr., 59, 5059 (1963)) and can be prepared with

  a high yield using acidic or basic catalysts.

  The acylation of hydroxychalcone (II) can be carried out using ordinary acylation reactions. For example, we can use a

  a process in which a carboxylic acid anhydride cor-

  corresponding [(R2CO) 20] with the compound II using pyridine or a sodium salt of the corresponding carboxylic acid, or a process in which an acid chloride (R2COC1) is reacted using catalysts

basic non-nucleophilic.

  In the compounds of general formula (I), R 1 is a hydrogen atom

  gene or a methyl group and R2 is a straight or branched chain aliphatic hydrocarbon radical containing from 2 to 24 and preferably from 4 to 20

carbon atoms.

  The absorbers of the UV rays according to the invention are obtained by

  addition in a conventional manner of the compound of the general formula (I) to

  known for cosmetics. Absorbers can be prepared in the form

  creams, solutions, oils, sprays, pencils, emulsions, bases and ointments.

  When the compounds of the invention are mixed with substrates for ointments or creams, oily or non-oily ointments or anti-tanning dermal creams are obtained. Likewise, when the compound is mixed with solvents (or emulsifiers as the case may be), anti-tanning oils, lotions or skin care creams are obtained. Among the substrates or solvents that can be used for this purpose, mention may be made of hydrocarbons such as solid or liquid paraffins, crystalline oil, ceresin, ozokerite and Montana wax; vegetable oils, oils and animal fats, for example olive oil and waxes such as mineral wax, carnauba wax, lanolin, spermaceti oil and

  like; aliphatic acids and their esters, such as stearic acids,

  palmitic and oleic, glycerol monostearate, distearate and monooleate, isopropyl myristate and stearate, butyl stearate and the like; and alcohols such as ethyl, isopropyl,

  cetyl, palmitilic, hexyldodecyl and the like.

  In addition, it is possible to use polyalcohols serving as humectants

  such as glycol, glycerin or sorbitol.

  The amount of the compound (I) in the UV absorbers may vary depending on the type of preparation and is therefore not critical. Although an effective amount of the compound (I) is sufficient, this amount is in

  general from 0.1 to 20%, preferably 0.5 to 10%, of the weight of the composition.

  Although the UV absorber of the invention may comprise only compound (I) as an active ingredient, it is preferred to use it in

  combination with other UV-B absorbers to obtain a cosmetic

  ordinary tick anti-tan. Examples of UV-B absorbers are: P-methylbenzylidene-D, L-camphor or its

  sodium 2-phenylbenzimidazole-5-sulfonate sodium, 3,4-dimethyl-

  sodium phenylglyoxylate, 4-phenylbenzophenone, 4-phenylbenzophenone-2'-

  isooctyl carboxylate, p-methoxycinnamate, 2-phenyl-5-methylbenzoxazole,

  p-dimethylaminobenzoate and the like.

  In addition to the above ingredients, ultraviolet absorbers

  violets according to the invention may also comprise various additives. Suitable additives are, for example, W / O and O / W emulsification agents. These emulsifying agents are commercially available. We can

  use thickeners or additives such as methyl-

  cellulose, ethylcellulose, carboxymethylcellulose, polyacrylic acid,

  gum tragacanth, agar-agar and gelatin. If necessary, we can

  perfumes, preservatives, humectants, stabi-

  emulsion leaflets, medicinal ingredients and / or physiological dyes

allowed.

  The following examples and reference examples, in which all proportions are by weight unless otherwise stipulated, serve to illustrate

  the invention without in any way limiting its scope.

  Experimental Example Creams comprising 2% of compounds of the invention are used to determine the protective effect of the skin against irradiation by UV-A rays. In this test, a cream having the composition of Example 9 (product of the invention 4) and creams in which is used, instead of 4-methoxy-4'palmitoyloxychalcone used in the composition of the Example 9, 4methoxy-4'-isotearoyl (methyl-branched) oxychalcone (product of the invention 1), 4-methoxy-4'-stearoyl

  (linear) oxychalcone (product of the invention 2), 4-methoxy-4'oleoyloxy

  chalcoe (product of the invention 3), 4-methoxy-4'-octanoyloxychalne

  invention 5), 4-methoxy-4'-hexanoyloxychalcone (product of the invention 6) or 4-methoxy-4'-propanoyloxychalcone (product of the invention

  7). The test protocol is that of Gschnait et al (Archives of Dermatology).

  Research 263, 181-188, 1978). Specifically, we shave the back of guinea pigs to expose the skin. The susceptibility to UV-A is increased by intracelial determination of 8-methoxypsoralen in guinea pigs. After that, the creams 1 to 7 according to the invention are applied to the exposed skin at the rate of 2 mg / cm 2

  and 15 minutes after the application, irradiation with UV-A is carried out.

  24 hours after irradiation, the skin is examined for the presence or absence of erythema and the shortest UV-A irradiation time is determined before erythema occurs on the skin. This shortest duration is compared to the shortest duration of UV-A irradiation before the development of erythema on untreated skin and the sun protection factor is calculated (abbreviated below). after SPF) according to the equation below, from which the protective effect of the skin by the respective compounds is determined. The comparison creams are a cream-only base (comparison product 1) used in

  Example 9 or Vaseline (Comparative Product 2).

  Shortest duration of irradiation with UV-A before development of erythema on the skin having received a cream application according to SPF = the invention SPF = Shortest duration of UV-A irradiation before development of a

  erythema on the skin that has not received cream.

  The results of this test show that the cream base alone or petrolatum can not protect the skin from UV light, but creams comprising 2% of the compounds according to the invention have FPS values.

  from about 6 to 8, effectively protecting the skin from UV-A rays.

  Reference Example Synthesis of 4-methoxy-4'-hydroxychalcone In an ethanolic solution (5 liters) comprising 500 g (3.67 moles) of anisaldehyde and 500 g (3.67 moles) of 4-hydroxyacetophenone, drop 600 ml of an aqueous solution of 250 g of sodium hydroxide in about 80 minutes in a stream of nitrogen. The mixture is then heated to 50 ° C. and

  it is stirred for 24 hours. The reaction mixture is cooled to room temperature.

  Ambient temperature and 2 liters of 12% hydrochloric acid and then 4 liters of water are added, whereupon crystals are deposited. The crystals were collected by filtration and washed rapidly with ethanol and then dried under reduced pressure to give 750 g (2.95 moles, 80% yield) of the title compound. The compound is recrystallized

  ethanol and purified prismatic crystals of a light yellow.

  The melting point and various spectral data of the compound coincide with

those of a reference compound.

  Melting point: 189.5 ° C (188 to 190 ° C for the reference compound)

Example 1

  Synthesis of 4-methoxy-4-isosterol, methyl-branched oxychalcone 10.17 g (0.04 mole) of 4-methoxy-4-hydroxychalcone obtained in the reference example and 6.33 g (0.080 mole) of pyridine are dissolved in 100 ml of methylene chloride previously dried with calcium chloride, and to this mixture is added dropwise 20 ml of a solution

  anhydrous in methylene chloride of isostearoyl chloride with branching

  methylation in 10 minutes under ice-cooling and stirring conditions. The mixture was allowed to stand at room temperature overnight and refluxed for 20 minutes to complete the reaction. The reaction mixture is poured into ice-cold water, then concentrated hydrochloric acid is added to acidify the mixture (pH = 1), and then extracted with chloroform. The chloroform phase is washed with a saturated aqueous solution of sodium bicarbonate,

  dry over anhydrous sodium sulphate and remove the solvent

  under reduced pressure in order to obtain the desired compound with a

  substantially quantitative yield. The melting point and the spectral data

  of the compound are shown in Tables I and II.

Examples 2 to 7

  The procedure is as in Example 1 but replacing the methyl-branched isostearoyl chloride respectively by propionyl chlorides, hexanoyl, octanoyl, palmitoyl, stearoyl, and oleoyl, to obtain the desired compounds. The melting points and various spectral data of these compounds also appear in Tables

I and II.

Table t

  Example Formula (1) Point of Yield Analysis uv (CUC13) lR (& me1, KBr) melting ('C) (%) elemental (Calc) xmax R1 R2CO Yc = o) loe R. HCO * C (%) H <%) (rim) ó (Zog) CO

1 CH3 C17H35CO 23100 1620, 1650

  [isost aroy) to methylammonium 40-50 100 341 (4t36) 1740 methyl) oxy]

  2 C2H5CO 87.0 - 8I75 80 73.41 6.14 341 21700 1625, 1660,

(73.53) (5 <85) (4.34) 1940

  3 C5HlCO 69> 2 - 69q5 82 74.92 6.86 341 22300 1620, 1650

<74.98) (6.86) (4935) 1740

  4 "C7H15CO 76> 3 - 76.7 95 75.80 7.29 341 22600 1620, 1650 <75.76) (7e42) (4.36) 1735

  C1SH31CO 93.0 - 94 95 77.93 8.92 341 25600 1625, 1650

(78.01) (9.00) (4.41) 1740

  6 C17H35C0 90> 3 - 91.4 89 78.38 9.31 341 22200 1625, 1650

(78.42) (9.29) (4.35) 1740

  7 # C1733C0 55.4 - 56/4 87 78098 8.66 341 22900 1625, 1655,

  (oleoyloxy) (78172) (8.94) (4.36) 1740

Table II

  Example Formula (I) NMR Data (CDC13, TMS Internal Standard) a) b) c) R1 R2CO OCH3 Ar-H C = CH -COR2 C17H35CO 6.87 (2H, d) 7.30 (1H, d) 0 , 6-2 0 (33H, m, -C15H33) 1 CH3 [Isotearoyl (ramified) -3.78 7.17 (2H, d) 7.80 (111, d) 2.56 (2H, t, J = 7.0 Hz, -CO-CH 2 -) meithyl cation) oxy] 7.55 (2H, d) 8.03 (2H, d) -1.6656 (2H, d) 7730 (1H, d 1724 (3H, m.p. t, J = 6.0Hz, -CH3) 2 "C2H5CO 3.80 7.17 (2H, d) 7.80 (1H, d) 2.58 (2H, q, J = 7.5Hz, -CO- CH2-) 7.54 (2H, d) 8; CH3) 3 - C5H11CO3; 797t17 (2H, d) 7.80 (1H, d) 0> 7-2.1 (6H, m, - (CH2) 3 -) 7.55 (2H, d) 2 , (211, t, J = 70Hz11, -CO-CH2-) 8.03 <(2H, d) 6) 87 (2H, d) 7.30 (1H, d) 0.88 (3H, t, J = 6.0 Hz, -CH 3) 4 C 7 11 15 CO 3.80 7117 (2H, d) 7.80 (1H, d) 0.72,1 (10H, m, - (CH 2) 5 -) 7.55 ( 2H, d) 2.55 (2H, t, J = 7.0Hz, -CO-CH 2 -) 8.03 (2H, d) 6.87 (2H, d) 7.30 (1H, d) O, 87 (3H, t, J = 6.0Hz, -CH3) "C15H31CO 3.81 7, 17 (2H, d) 7.80 (1H, d) 0.7-2.1 (26H, m, - ( CH 2) 13-) 7> 55 (2H, d) 2.55 (211, t, J = 7.0Hz, -CO-CH 2 -) 8503 (2H, d) 67 (2H, d) 7.30 ( 1H, d) 0.86 (3H, t, J = 6; 0Hz, -CH 3) 6 "C 17 H 35 CO 3) 80 7.17 (2H, d) 7.80 (1H, d) 0.6-2.1 (301, m, (CH 2) 15 -) 715 (2H, a) ) 2.56 (2H11, t, J = 710Hzt-CO-CH2-) 8; 03 (2H, d) 6, 87 (2H, d) 7H (30H), d) 0.89 (3H, t, J) = 6.0 Hz, -CH 3) 7 "C 17 H 33 CO 3,83 7,17 (2H, d) 7.80 (1H, d) 0.7-2.5 (2811, m, -C 15 H 28 -) (oleoyloxy) 7 , 55 (2H, d) 2556 (2H, t, J = 70Hz, -CO-CH 2 -) r 8.03 (2H, d) aLA

a) 3H, s. b) J = 8.SHz. c) J = 16Hz.

o0,

Example 8

  Cream type O / E A composition of the following formula is prepared by proceeding in a

  usual to obtain a cream type O / W.

  [Composition] 4-Methoxy-4'-isostearoyl (methyl-branched) Oxychalcone 2.0 (wt%) Stearic acid 1.0 Oleophilic monostearic glyceride 2.0 Polyoxyethylene sorbitan monostearate 1.0 Cetyl alcohol 1.0 Alcohol Stearyl 1.0 Squalane 10.0 Liquid paraffin 20.0 Vaseline 5.0 Butylparaben 0.1 Methylparaben 0.1 Triethanolamine 1.0 Glycerine 10.0 Perfume Quantity suitable for use Water Supplement, 0

Example 9

  E / H type cream A composition of the following formula is used to prepare a

E / H type cream.

  [Composition] 4-Methoxy-4'-palmitoyloxychalcone 2.0 (wt.%) Sorbitan sesquioleate 4.0 Aluminum stearate 0.5 Cetyl alcohol 4.0 Liquid paraffin 16.0 Squalane 10.0 Isopropyl myristate 5.0 Sodium Benzoate 0.3 Glycerine 10.0 Fragrance Proper Amount Water Supplement, 0

Example 10

  O / W emulsion A composition of the following formula is used to prepare an O / W type emulsion [Composition] 4-Methoxy-4'-octanoyloxychalcone 3.0 (wt.%) Stearic acid 2.0 Sorbitan monostearate 1.5 Polyoxyethylene sorbitan monostearate 1.0 Cetyl alcohol 0.4 Stearyl alcohol 0.3 Isopropyl myristate 7.0 Squalane 5.0 Liquid paraffin 5.0 Solid paraffin - 2.0 Ethylparaben 0.1 Methylparaben 0.1 Carbopol 0.2 Caustic potash o, 4 Fragrance Proper quantity Water Complement, 0

Example 11

  Lotion A composition of the following formula is used to prepare a lotion. [Composition] 4-Methoxy-4'-hexanoyloxychalcone 2.0 (wt%) (Product of the Invention) Polyoxyethylene (23) Ether Ether 4.0 Ethanol 10.0 Glycerin 3, Dipropylene Glycol 7.0 Lactic Acid 0.05 Sodium lactate 0.12 Methylparaben 0.1 Fragrance Proper amount Colorant Small amount Water Supplement, 0

Claims (2)

  1. Chalcone derivative, characterized in that it corresponds to the general formula (I) R10) .CH = CH: -C O-C- \ R2) \ -3- / l 0 0   wherein R 1 represents a hydrogen atom or a methyl group and R represents a straight chained aliphatic hydrocarbon radical or   branched containing from 2 to 24 carbon atoms.   2. Absorber of ultraviolet rays, characterized in that it com-   takes an effective amount of an ehalcone derivative as defined in the claim 1.